Ch. 9 Immunologic Tolerance and Autoimmunity

Flashcards covering the mechanisms of immunologic tolerance, T and B cell selection, regulatory mechanisms, and the development of various autoimmune diseases based on lecture notes.

Immunologic Tolerance

A state of unresponsiveness to a self-antigen, which is an essential feature of the normal immune system to prevent self-destruction.

Immunogenic response

Antigen recognition that leads to lymphocyte activation, resulting in proliferation and differentiation into effector and memory cells, typically in response to microbes.

Immunologic Ignorance

A response where an antigen is ignored by an antigen-specific lymphocyte, typically occurring with self-antigens.

Tolerogenic response

Antigen recognition that leads to the lymphocyte becoming nonfunctional or killed, typically in response to self-antigens.

Central Tolerance

Immunologic tolerance induced when developing lymphocytes encounter self-antigens in generative lymphoid organs, such as the bone marrow for B cells and the thymus for T cells.

Peripheral Tolerance

Tolerance induced and maintained when mature lymphocytes encounter self-antigens in peripheral lymphoid organs or peripheral tissues.

Negative Selection

The principal mechanism of central tolerance in T cells where immature thymocytes that recognize self-peptide:MHC complexes with high affinity die by apoptosis.

AIRE (autoimmune regulator)

A gene that encodes a transcriptional regulatory protein enabling the expression of many peripheral tissue self-antigens by thymic epithelial cells for T cell selection.

Autoimmune polyendocrine syndrome (APS-1)

A rare disorder caused by mutations in the AIRE gene, leading to the failure of T cell elimination and lack of regulatory T cell development for several tissue antigens.

Anergy

A state of long-lived functional unresponsiveness induced in T cells when they recognize antigens without adequate costimulation.

CTLA-4

An inhibitory receptor on T cells that competitively inhibits the B7-CD28 interaction and removes B7 molecules from the surface of APCs to block T cell activation.

PD-1

An inhibitory receptor expressed on T cells after antigen stimulation that activates a phosphatase to inhibit signals from the TCR complex and CD28.

Checkpoint blockage

A cancer therapy that uses antibodies to block inhibitory receptors like CTLA-4 and PD-1 to enhance antitumor immune responses.

Regulatory T cells (Tregs)

A population of CD4+ cells, typically expressing CD25 and CTLA-4, that suppress the activation of potentially harmful self-reactive lymphocytes.

FOXP3

The transcription factor that controls the development and function of regulatory T cells (Tregs).

IPEX syndrome

A systemic, multiorgan autoimmune disease resulting from mutations in the FOXP3 gene and a subsequent lack of FoxP3+ Tregs.

IL-2

A cytokine required for the generation and maintenance of functional Treg cells, while also promoting immune responses by stimulating T cell proliferation.

ALPS (Autoimmune lymphoproliferative syndrome)

A collection of diseases characterized by defects in apoptosis caused by mutations in the FAS gene or genes encoding caspase-8 or caspase-10.

Receptor Editing

A process in central B cell tolerance where immature B cells that recognize self-antigens re-express RAG genes to change their light chain and produce a new Ig receptor.

Molecular Mimicry

A phenomenon where microbial antigens cross-react with self-antigens because of structural similarities, leading to an immune response against self-tissues.

Rheumatic Fever

A transient autoimmune disease caused by molecular mimicry where anti-streptococcal antibodies cross-react with myocardial proteins.

Citrullination

The enzymatic conversion of arginine to citrulline in self-proteins, creating neoantigens that are recognized as non-self in rheumatoid arthritis.

Rheumatoid Factor

IgM, IgG, or IgA autoantibodies specific for the Fc portion of IgG, often found in patients with rheumatoid arthritis.

Sympathetic Ophthalmia

An autoimmune reaction against both eyes following trauma to one eye, caused by the release of sequestered eye antigens that were previously hidden from the immune system.

Systemic Lupus Erythematosus (SLE)

A systemic autoimmune disease characterized by the production of antibodies against self-nucleic acids and nucleoproteins (ANAs).

HLA-B27

An MHC allele that increases the relative risk of developing ankylosing spondylitis by $90-100$ times.

PTPN22

A tyrosine phosphatase gene polymorphism associated with uncontrolled activation of B and T cells and linked to rheumatoid arthritis, SLE, and type 1 diabetes.